Skeletal muscle atrophy diminishes the health and quality of life of tens of millions of people in the US alone. Frequent causes of muscle atrophy (which often co-exist in the same patient) include aging, malnutrition, muscle disuse, critical illness, certain medications, and a broad range of chronic illnesses including cancer, heart failure, COPD, diabetes, renal failure, cirrhosis, rheumatoid arthritis, and HIV/AIDS. Frequent effects of muscle atrophy include weakness, impaired activity, falls, prolonged hospitalization, delayed rehabilitation, loss of independent living, and increased mortality. However, despite its broad clinical impact, skeletal muscle atrophy lacks a medical therapy and thus represents an enormous unmet medical need. A major goal of Emmyon, Inc. is to discover and develop a pharmaceutical for skeletal muscle atrophy. In our Phase I STTR project, we designed and synthesized a series of novel chemical entities (NCEs), which were then subjected to primary screening in cultured skeletal myotubes, followed by secondary investigations in a mouse model of immobilization-induced muscle atrophy. Through these studies, we discovered (and subsequently patented) a confidential and proprietary small molecule compound (EMMY1-19) that potently and effectively reduces skeletal muscle atrophy in vivo. In this Phase II SBIR proposal, Emmyon seeks to advance the development of EMMY1-19 and related molecules as pharmaceuticals for skeletal muscle atrophy. Specifically, we will further investigate EMMY1-19's safety, efficacy, and mechanisms of action in two distinct and complimentary mouse models of muscle atrophy (immobilization-induced and age-related muscle atrophy); together, these studies will significantly advance our understanding of EMMY1-19 and, if successful, significantly advance EMMY1-19 towards final development and commercialization in SBIR Phase III. In parallel to those studies, we will design and synthesize a new and expanded series of 200 additional NCEs, which will be screened and compared to EMMY1-19 in cultured human skeletal myotubes and mouse models of skeletal muscle atrophy; through these studies, we hope to identify additional NCEs with pharmacologic properties that are similar to or perhaps even better than those of EMMY1-19. Altogether, through these studies, we hope to rigorously advance the scientific understanding and commercial development of a highly promising new class of pharmaceutical agents for skeletal muscle atrophy.